This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: Cancers of the oral cavity and pharynx represent approximately 2.5% of all cancers in the United States, with an estimated 35,310 new cases and 7,590 deaths in 2008. Oral squamous cell carcinomas (OSCCs) are the most common form of oral cancer. It has a very poor prognosis if diagnosed at advanced stages;but even when diagnosed at earlier stages, the treatment results in poor quality of life due to radical resection often necessary. Increased levels cytokine expression by tumor cells is considered fundamental both to tumor initiation and progression because it affects critical cellular processes, including proliferation and metastasis. Rationale: Cytokine expression is controlled by an intracellular signaling mechanism, which has many self-regulatory processes to limit their expression to the minimum length of time necessary. One of these mechanisms is represented by a group of proteins called suppressor of activated cytokine signaling (SOCS). There is evidence that expression of these self-regulatory proteins is defective in various types of cancer, but there is not much information available on the role of these proteins in OSCC. Design and outcomes: Presence and levels of SOCS1 and SOCS3 proteins will be detected in tissue samples of OSCC cases and also in normal tissue samples. The presence and levels of expression will then be correlated to the tumor stage and progression status to find out if there is a defect on this self-regulatory mechanism in tumor cells. Additional experiments conducted in the laboratory using culture of human cancer cell lines will both increase and inhibit the expression of SOCS proteins and evaluate their role on tumor cell proliferation, invasive capacity and cell survival.